Identification of novel promising HDAC2 inhibitors beyond hydroxamates: A rational pharmacophore-driven computer aided drug design study

Introduction

Histone deacetylase 2 (HDAC2) plays a pivotal role in the progression of several cancers and non-malignant diseases, making it an attractive therapeutic target. Although significant efforts have been directed toward the development of HDAC2 inhibitors, the clinical utility of hydroxamate-based scaffolds is limited by their well-documented adverse effects. Consequently, the discovery of non-hydroxamate HDAC2 inhibitors remains a critical unmet need.